Every year approximately 24,000 patients develop new cancers of the oral cavity. If the larynx and skin are excluded, the oral cavity is the most common site for squamous carcinoma arising in the head and neck. During the past few years experimental evidence has accumulated which indicates that some metabolites of arachidonic acid, particularly the primary prostaglandins, are involved in mechanisms of initiation, promotion, and growth of tumors. Further, manipulation of PG synthesis with analogs and inhibitors will influence the development of tumors. There is impressive evidence that supports the conclusion that vit A is a natural inhibitor for the development of cancer. It seems clear that the retinoids have the potential to prevent the progression of premalignant disorders into malignant disease. The polyunsaturated fatty acids linoleic, gamma-linolenic, and eicosapentaenoic, as well as PGE1 and PGA1 have shown to suppress significantly the proliferation rate of a number of malignant cell lines in culture. The overall objectives of this pilot study are to investigate the effect of some retinoids (All-trans-B-retinoic acid, 13-cis-retinoic acid, B-retinyl acetate, vit A, and 4-hydroxyphenyl retinamide), and polyunsaturated fatty acids on the biosynthesis of PGE2 by three head and neck squamous carcinoma cell lines, and normal human gingival fibroblasts in culture. After incubation of the cells for 24 hrs with or without the reagents, the supernatants of incubation media are extracted, at pH 3, with organic solvents and PGE2 in determined by radioimmunoassay or radiometric assay as described under methods. The information gained from this research will be most valuable since there are no reports in the literature on the comparative effects of retinoids and polyunsaturated fatty acids on PG synthesis by human cancer and normal cells, simultaneously. The results will also provide information about whether the PGs are involved in the action of the agents mentioned on cancer and normal cells.